Beyond our eyes: the non-visual impact of light

Christian Cajochen, PhD Centre for Psychiatric Hospital of the University of Basel, Switzerland

SLL-erate final event October 13, 2016, Brussels Thomas Edison was maybe wrong !

Artificial outdoor nighttime lights associate with altered behavior in the American general population (n=19’136) Distribution of nighttime radiance calibrated lights

Ohayon and Miles, Sleep, 2016 Light is the most important !

Buttgereit, Smolen, Coogan, Cajochen, Nat Rev Rheumatol, 2015 Light and human circadian rhythms as the best circadian marker in humans

Induction of a Phase Delay in the Human Circadian Melatonin Rhythm by Light (10’000 lux for 6.5 h)

Midpoint Midpoint 4:45 8:21

400

Light /L)

300 pMol

200

100 Plasma Melatonin ( Melatonin Plasma 0 12 24 12 24 12 24 12 24 12 Time of Day

Sleep period Khalsa et al., J Physiol (London) 2003 Light and circadian phase Phase-Response Curve

4 3

2 (h) 1 shift 0

-1 Phase Phase -2

-3 6.7 hours 10’000 lux -4 polychromatic whiteRetina light -18 -15 -12 -9 -6 -3 0 3 6 9 12 15 18 Initial Phase (time relative to DLMO=0)

Khalsa, et al., J Physiol (London) 2003 «Light impacts on our circadian rhythms more powerfully than any drug»

Charles Czeisler «Casting light on sleep deficiency» Nature, 2013 Suppression of melatonin in a totally blind person with bright light

Sighted Person 300

200 Plasma Melatonin 100 (pmol/liter)

37.5

37.0 Core Body Temperature 36.5 (°C)

36.0 12 18 24 6 12 18 24 6 12 Time of Day (h) Blind Person 300

200 Plasma Melatonin 100 (pmol/liter)

37.5

37.0 Core Body Temperature (°C) 36.5

36.0 12 18 24 6 12 18 24 6 12 Time of Day (h) Czeisler et al., New Engl Med 1995 Light is more than vision non-visual / non-image forming light effects

Light can be «seen» without conscious vision

«Forced choice» test in a totally blind person

100 *

80

60

40

Correct Answer (%) 20

0 420 460 481 500 506 515 540 560 580 Wavelength (nm)

Nach Zaidi et al., Curr Biol, 2007 Non-classical Photoreceptor intrinsic photosensitive retinal ganglion SCN cells (iPRGs, ) (circadian Pacemaker)

Eye A dual sensory organ

Rods

Retina Cones

Hattar et al. Science, 2002 Berson et al. Science, 2002 Light and circadian phase Phase-Response Curve

4 3

2 (h) 1 shift 0 -1 Phase Phase 75 % of the resetting -2 response

-3 6.7 hours 10’000 lux -4 polychromatic whiteRetina light 6.5 hours blue light (480 nm) -18 -15 -12 -9 -6 -3 0 3 6 9 12 15 18 11.8 μWcm−2, 11.2 lux) Initial Phase (time relative to DLMO=0)

Khalsa, et al., J Physiol (London) 2003 Rüger, et al., J Physiol (London) 2013 Effects of LED-backlit computer screens on salivary melatonin, alertness and cognitive performance in the evening

Cold Cathode Fluorescent Lamp Salivary Melatonin (CCFL)

Light Emitting Diode 10 (LED )

8

Non-LED Screen

6

Baseline  ~ 60 min Dark Dark Adaptation

pg/ml 4

2 LED Screen

0 * * * * 18:15 19:15 20:15 21:15 22:15 23:15 00:15 * p<0.04; Duncans‘ multiple range test

Time of Day (h) Cajochen et al., J Appl Physiol. 2011 Smartphone use in adolescents (14-20 years)

Use of smartphones Where do you keep your smartphone during night? 1 hour prior bedtime

irgendwo in der Wohnung 14% 23% irgendwo im Zimmer 99 % Ja auf dem Nachttisch nicht beantwortet im Bett 60% 99% yes nicht beantwortet

97% in bedroom How often do you use your smartphone after «Lights off»

10% nie 15% selten 49% gelegentlich häufig 25% nicht beantwortet Strube et al. Somnologie, 2016 74% occasionally-often “Ipad” versus “Blue-blockers” Transmission Spectra

1.0

0.8

0.6

0.4

0.2 Relative Amplitude Relative

0 400 450 500 550 600 650 700 Wavelength iPad Orange-tinted glasses (blue blockers) Evening Melatonin Levels in Adolescents

Dim Dark LED/glasses Dim

* Blue Blockers for one week 16 Clear Lenses for one week 14 * * 12

*

10

8

pg/ml Sleep 6

4

2

0

Time of day

van der Lely et al., J Adolesc Health, 2014 Light has also «non-circadian» acute effects

• Light suppresses the soporific hormone melatonin within minutes (Gronfier et al., 2002)

• Light inhibits sleep-promoting GABA neurons in the ventrolateral preoptic area in the hypothalamus (VLPO, Tsai et al., 2009)

• Light activates wake-promoting orexin neurons in the lateral hypothalamus (McGregor et al., 2011) Acute sleep induction by light in nocturnal mice

Lights ON Lights OFF 60 Wildtype Melanopsin knockout

Melanopsin aDTA

30

Response (min) Response

Sleep

0 0 1 2 3 Time elapsed from light onset (h)

According to Muindi et al., Front Syst Neurosci, 2014 Acute alerting effects of light in diurnal humans Subjective Alertness

5

10

more alert more 15

20

120 lux !

25

10 100 1000 10000

Illuminance (lux) Cajochen et al., Beh Brain Res. 2000 Karolinska Sleepiness Scale (KSS) 8 6 7

Monochromatic The human

light alerting

% Sleepiness Change

0 = pre-light response 10 20 30 40 50 Energy 0

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to Book chapter, Book Springer,2014 et alCajochen

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is ., Sleepiness and human impact impact assessmenthumanSleepiness and .,

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Karolinska Sleepiness Scale (KSS) - 4 5 6 shifted

Computer Screens

KSS-score 2 3 4 5 6 7 8

*

Subjective Sleepiness in Adolescents Dim Blocking blue light intheevening

Dark

LED/glasses Time of of day Time *

* Sleep Sleep Dim van2014 Health, Lely Adolesc etJ der al.,

Clear Lenses for week one Clear Lenses Blue Blockersfor Blue week one

Does light affect higher cognitive functions ?

Does light make you bright? Sustained Attention and Response Control (Go/noGo Task)

Letter „W“: go

Letter „M“ : no-go

90

faster

95

LED Screen Baseline

100 Dark Adaptation

105

Relative Reaction Time (%) Time Reaction Relative

* Non-LED* Screen

slower 110 * P <0.05 18:15 19:15 20:15 21:15 22:15 23:15 00:15

Monitor: F1,11=12.2; p<0.04 Time of day: F11,44=7.8; p<0.02 Time of Day (h) Monitor x Time: F12,132=3.0; p=0.041 Cajochen et al., J Appl Physiol. 2011 Declarative Learning (Word pairs)

Correctly identified word pairs Correctly identified new word pairs

70 70 * 65 65

60 60

% 55 55

50 50

45 45

LED Screen * P <0.05 Non-LED Cajochen et al., J Appl Physiol. 2011 Light is not just for vision

Cortex Thalamus Hypothalamus Brainstem - Locus coeruleus

Limbic system - Amygdala - Hippocampus

Modified from Vandewalle et al. Trends Cogn Sci, 2009 Light has many non-visual biological effects in humans (only peer reviewed data)

• Synchronization of circadian rhythms

• Suppression of the «darkness hormone» melatonin

• Alerting and enhancing of cognitive performance

• Regulation of pupil size

• Enhancing mood (antidepressant)

• Enhancing physical performance in top athletes

• Light color modulates mental effort

Conclusion

• Light rules our body via its non-visual effects

• Blue wavelengths -- which are beneficial during daylight hours because they boost attention, reaction times, mood, and physical performance -- are most disruptive at night

• The proliferation of electronics with screens, as well as energy-efficient lighting, is increasing our exposure to blue wavelengths, especially after sundown Non-visual lighting solutions should be:

Dynamic • Intensity and duration • Spectral composition • According to time of day

Individual • Age • Gender • Chronotype (early vs.late people) Wanted

Intelligent human centric lighting to adapt our illuminated surroundings such that we do not jeopardize quality of life and health but positively influence our sleep, circadian physiology, cognition and well-being

Human Centric Lighting

enter the room by

Human centric lighting supports your health and promotes Acknowledgements

Centre for Chronobiology www.chronobiology.ch

• Antoine Viola, PhD • Christina Schmidt, PhD • Mirjam Münch, PhD • Sarah Chellappa, PhD • Vivien Bromundt, PhD • Jakub Späti, PhD • Sylvia Frey, PhD • Virginie Gabel • Micheline Maire • Carolin Reichert • Stephanie van der Lely

EU IP Swiss Federal Office for Public Health Daimler-Benz Foundation